Back to resultsPhase II Study of Nivolumab in Combination With Radiation Therapy as Definitive Treatment for Patients With Locally Advanced, Unresectable Head and Neck Mucosal Melanoma.
Primary Purpose
Melanoma
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nivolumab
Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 19 years
- Histologically or cytologically confirmed mucosal melanoma of head and neck
- Locally advanced and unresectable
- No previous chemotherapy for purpose of palliation
- ECOG performance status of 0~2
- Measurable lesion per RECIST 1.1 criteria
- Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained endoscopic biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
- Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
- Collection of an archived tissue sample will also be requested (where available) to support evaluation of the clinical utility of biomarker assessment in newly obtained vs. archived tissue samples; however, a subject will not be precluded from participating in the study if an archived tissue sample is not available for collection or is otherwise insufficient for analysis.
- Adequate marrow, hepatic, renal and cardiac functions:
Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin ≤ 1.5 x ULN Absolute neutrophil count (ANC) ≥ 1,500/uL Platelets ≥ 100,000/uL Hemoglobin ≥ 8.0 g/dL Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) Serum creatinine ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Creatinine clearance should be calculated per institutional standard.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 8.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- provision of a signed written informed consent
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Active or history of autoimmune disease or immune deficiency, including MG, myositis, hepatitis, SLE, RA, IBD or GBS)
- Severe co-morbid illness and/or active infections
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has a known history of active TB (Bacillus Tuberculosis)
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Pregnant or lactating women
- History of documented congestive heart failure; angina pectoris requiring medication; evidence of tranasmural myocardial infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; or high risk of uncontrollable arrhythmia
- Active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
- Must not have undergone a major surgical procedure < 4 weeks or radiotherapy <2 weeks prior to D1 of treatment
- Administration of a live, attenuated vaccine within 4 weeks before study treatment
- Treatment with systemic immunosuppressive medication (including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 2 weeks prior to D1 of treatment
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nivolumab
Arm Description
Nivolumab 3mg/kg + NS 100mL MIV over 1hr every 2 weeks
Outcomes
Primary Outcome Measures
Response rate
RR, as determied by irRECIST criteria, is defined as the proportion of all subjects whose best overall response (BOR) is either a CR or PR. BOR is determined by the best response designation recorded between the date of treatment initiation and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever is the first. For subjects without documented progression or subsequent anti-cancer therapy, all available repsonse designations will contribute to the BOR determination.
Secondary Outcome Measures
Full Information
NCT ID
NCT03758729
First Posted
November 28, 2018
Last Updated
February 14, 2021
Sponsor
Samsung Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03758729
Brief Title
Phase II Study of Nivolumab in Combination With Radiation Therapy as Definitive Treatment for Patients With Locally Advanced, Unresectable Head and Neck Mucosal Melanoma.
Official Title
Phase II Study of Nivolumab in Combination With Radiation Therapy as Definitive Treatment for Patients With Locally Advanced, Unresectable Head and Neck Mucosal Melanoma.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Internal Issues
Study Start Date
May 2020 (Anticipated)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 11, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 2, single center study to evaluate the efficacy, safety of nivolumab in combination with radiation therapy in patients with mucosal melanoma of the head and neck (MMHN). Target Accrual and Study duration We will accrue up to 26 patients. It is estimated to take up to 2 years. The sample size is calculated by use of SWOG CRAB (Cancer Research And Biostatistics) to control the type I error at 5 % for null hypothesis that the true response rate was 25 % or below and to have 80 % of power if the true response rate was 50 % or higher. Although the target number of evaluable patients is 23, we planned to recruit 10% more than the target number of patients considering dropout, total 26.
Detailed Description
This is a phase II, single-arm, single-center study to evaluate the response rate, efficacy and safety of nivolumab in combination with radiation therapy in subjects with of locally advanced, unresectable head and neck mucosal melanoma.
A cycle is defined as 14 days. The nivolumab dose will be fixed at the recommended phase II dose of 3mg/kg as a 60-minute IV infusion every two weeks. Patients will continue on nivolumab up to 8 weeks, until disease progression, unacceptable toxicity, investigator's decision to remove patient from the study, patient refusal to continue, or alternative treatment.
Concurrent radiotherapy of 70Gy for 6-7 weeks will be initiated on the same day of first nivolumab dose of cycle 1.
The combination of 70 Gy radiotherapy for 6-7 weeks begins on the day of initial administration of nivolumab, radiation therapy dose and treatment schedule 2.0, based on NCFC practice.
Nivolumab is administered every two weeks in in combination with radiation therapy and has elapsed since 8 weeks (after 4 cycles) The administration of clinical trials in is terminated but nivolumabs is sustainable at the discretion of investigator. (This is carried out independently of the clinical trial) The response rate of radiation therapy is assessed by performing a tumor assessment every two months up to the end of radiation therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nivolumab
Arm Type
Experimental
Arm Description
Nivolumab 3mg/kg + NS 100mL MIV over 1hr every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
Nivolumab 3mg/kg + NS 100mL MIV over 1hr every 2 weeks
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
Radiation Therapy
Primary Outcome Measure Information:
Title
Response rate
Description
RR, as determied by irRECIST criteria, is defined as the proportion of all subjects whose best overall response (BOR) is either a CR or PR. BOR is determined by the best response designation recorded between the date of treatment initiation and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever is the first. For subjects without documented progression or subsequent anti-cancer therapy, all available repsonse designations will contribute to the BOR determination.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 19 years
Histologically or cytologically confirmed mucosal melanoma of head and neck
Locally advanced and unresectable
No previous chemotherapy for purpose of palliation
ECOG performance status of 0~2
Measurable lesion per RECIST 1.1 criteria
Be willing to provide fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained endoscopic biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
Collection of an archived tissue sample will also be requested (where available) to support evaluation of the clinical utility of biomarker assessment in newly obtained vs. archived tissue samples; however, a subject will not be precluded from participating in the study if an archived tissue sample is not available for collection or is otherwise insufficient for analysis.
Adequate marrow, hepatic, renal and cardiac functions:
Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin ≤ 1.5 x ULN Absolute neutrophil count (ANC) ≥ 1,500/uL Platelets ≥ 100,000/uL Hemoglobin ≥ 8.0 g/dL Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) Serum creatinine ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Creatinine clearance should be calculated per institutional standard.
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 8.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
provision of a signed written informed consent
Exclusion Criteria:
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Active or history of autoimmune disease or immune deficiency, including MG, myositis, hepatitis, SLE, RA, IBD or GBS)
Severe co-morbid illness and/or active infections
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Has a known history of active TB (Bacillus Tuberculosis)
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Pregnant or lactating women
History of documented congestive heart failure; angina pectoris requiring medication; evidence of tranasmural myocardial infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; or high risk of uncontrollable arrhythmia
Active CNS metastases not controllable with radiotherapy or corticosteroids (however, CNS metastases (except for leptomeningeal seeding) are allowed if controlled by gamma knife surgery or surgery or radiotherapy or steroid)
Must not have undergone a major surgical procedure < 4 weeks or radiotherapy <2 weeks prior to D1 of treatment
Administration of a live, attenuated vaccine within 4 weeks before study treatment
Treatment with systemic immunosuppressive medication (including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 2 weeks prior to D1 of treatment
12. IPD Sharing Statement
Learn more about this trial
Phase II Study of Nivolumab in Combination With Radiation Therapy as Definitive Treatment for Patients With Locally Advanced, Unresectable Head and Neck Mucosal Melanoma.
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